Grain legumes are a valuable source of food proteins. Their exploitation is expected to grow in relation of a growing world's food needs. Moreover, it is currently taking place a reappraisal of the beneficial effects of legume seed dietary intake, which are the basis for various health claims. Proteins and peptides concur to the observed biological activities of legume seeds, but their effect(s) has(ve) not completely been disclosed. Aims of this review are: to report the most relevant putative positive effects of grain legumes on human health and to give an account of the current knowledge on the demonstrated legume seed protein biological activities. Specific effects on the prevention and treatment of various diseases, mostly of which are typical of the affluent countries, are reported. Examples of studies at molecular level aimed at elucidating of the underlying mechanism(s) are given. The prospects on targeted legume protein exploitation in the nutraceutical area, including the biotechnological approaches, are also considered.